14-20412001-T-C

Variant names:

• chr14-20412001-T-C
• rs2184282
• NM_007110.5:c.-25+1404A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007110.5(TEP1):​c.-25+1404A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,070 control chromosomes in the GnomAD database, including 1,459 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1459 hom., cov: 31)
• Consequence: TEP1 NM_007110.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.689
• Publications: 9 publications found

Genes affected

TEP1 (HGNC:11726): (telomerase associated protein 1) This gene product is a component of the ribonucleoprotein complex responsible for telomerase activity which catalyzes the addition of new telomeres on the chromosome ends. The telomerase-associated proteins are conserved from ciliates to humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TEP1 Gene-Disease associations (from GenCC):

• cerebral palsy

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007110.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	NM_007110.5	MANE Select	c.-25+1404A>G		intron	N/A	NP_009041.2
	TEP1	NM_001319035.2		c.-25+1404A>G		intron	N/A	NP_001305964.1	G3V5X7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	ENST00000262715.10	TSL:1 MANE Select	c.-25+1404A>G		intron	N/A	ENSP00000262715.5	Q99973-1
	TEP1	ENST00000556935.5	TSL:1	c.-25+1404A>G		intron	N/A	ENSP00000452574.1	G3V5X7
	TEP1	ENST00000555727.5	TSL:1	n.-25+1404A>G		intron	N/A	ENSP00000451634.1	G3V470

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20344 AN: 151950 Hom.: 1453 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.128

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.134 AC: 20366 AN: 152070 Hom.: 1459 Cov.: 31 AF XY: 0.134 AC XY: 9945 AN XY: 74350

African (AFR) AF: 0.150 AC: 6213 AN: 41474

American (AMR) AF: 0.115 AC: 1751 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1193 AN: 5170

South Asian (SAS) AF: 0.107 AC: 518 AN: 4824

European-Finnish (FIN) AF: 0.128 AC: 1355 AN: 10568

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8631 AN: 67974

Other (OTH) AF: 0.130 AC: 275 AN: 2108

Alfa AF: 0.126 Hom.: 2343

Bravo AF: 0.132

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.81
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2184282; hg19: chr14-20880160;